March 27, 2017
Eli Lilly issued results of a phase III trial of abemaciclib in combination with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy. The global, double-blind study had an intent-to-treat population of 669 patients randomized to receive abemaciclib or placebo orally twice a day on a continuous dosing schedule, given in combination with fulvestrant at its approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study. The most common adverse events observed were diarrhea, neutropenia, nausea and fatigue, and were consistent with the previous studies of abemaciclib. Lilly intends to submit a new drug application (NDA) for single-agent abemaciclib in the second quarter of 2017.
February 21, 2017
ASLAN Pharmaceuticals issued results of a phase II study of varlitinib (ASLAN001) in combination with capecitabine as second-line treatment for metastatic HER2-positive breast cancer patients progressing on trastuzumab (Herceptin). The multinational, randomized, open-label study compared the effects of varlitinib combined with capecitabine versus that of lapatinib (Tykerb) combined with capecitabine on tumor shrinkage at week 12. Top-line data showed significantly greater tumor shrinkage at week 12 of the treatment cycle in patients who were on therapy for more than a month, receiving 400mg varlitinib (36.4%) twice daily compared to 1,250mg lapatinib (17.8%) once daily (p=0.075). A total of 50 patients were enrolled in the study. While the study was not powered for objective response rate (ORR), it found that patients dosed with varlitinib showed higher ORR compared to patients on lapatinib (60% versus 46%). There were no differences in progression-free survival (PFS) or overall survival (OS) in the study. Adverse events reported included nausea, vomiting and diarrhoea, and occurred at similar frequency in both arms. The incidence of grade three diarrhea was 12.5% in the varlitinib group and was clinically manageable. There were no instances of grade four diarrhea.
November 2, 2015
Immunomedics has reported results of
a phase III trial of sacituzumab govitecan
for metastatic triple-negative breast (TNBC),
small-cell (SCLC) and non-small-cell lung
(NSCLC) cancers. At the time of analysis, 56
enrolled patients had received sacituzumab
govitecan at the optimal dose of 10mg/kg
given on days one and eight of a three-week
cycle. Treatment response was available for
52 patients. The objective response rate was
29% (15/52), with two confirmed complete
responses. The interim median progression-free
survival (PFS), a measure of time patients
are living without their cancer progressing,
was seven months. Forty-six percent of these
TNBC patients had experienced a PFS event.
Overall survival (OS) data were too early to
report because 86% of patients are still alive.
For metastatic lung cancers, 33 patients with
NSCLC were enrolled to receive sacituzumab
govitecan at the 8.mg/kg or 10mg/kg dose
level. Among 29 patients assessable, an
objective response rate of 28% (8/29) was
observed, including patients with both squamous
cell and adenocarcinoma NSCLC types.
For the 25 patients at the 10mg/kg dose, the
interim median PFS was 3.8 months, with
48% of patients in this dose group having
experienced a PFS event. In SCLC, of the 27
patients enrolled at doses of 8mg/kg and
10mg/kg, 25 were assessable for response.
Six patients achieved a partial response (objective
response rate=24%). Interim median
PFS for the 12 patients at the 10mg/kg dose
level was 3.6 months and 83% of patients
had experienced a PFS event. Since 96% of
NSCLC patients and 100% of SCLC patients
were still alive at the time of analysis, OS
data at the optimal dose of 10mg/kg are too
early to report. Sacituzumab govitecan has
received Fast Track designation from the FDA
for the treatment of patients with TNBC, SCLC
and NSCLC, and also has been designated an
orphan drug for SCLC or pancreatic cancer
in the U.S., and for the treatment of patients
with pancreatic cancer in the E.U.
June 29, 2015
Genentech released results of a phase II study
of Perjeta (pertuzumab) in combination with
Herceptin (trastuzumab) and docetaxel
chemotherapy for HER2-positive early breast
cancer (eBC). The randomized, multicenter,
international study enrolled 417 people with
newly diagnosed HER2-positive, operable, locally
advanced or inflammatory eBC. Participants
were randomized to one of four study arms
and received four cycles (12 weeks) of neoadjuvant
treatment followed by surgery and a
year of adjuvant treatment with Herceptin plus
chemotherapy. Both progression-free survival
(PFS) and disease-free survival (DFS) were evaluated
at three years. The results suggested that
people who received the Perjeta regimen prior
to surgery were 31% less likely to experience
disease worsening, recurrence or death (PFS
HR=0.69; 95% CI, 0.34–1.40) compared to those
who received Herceptin and chemotherapy.
People treated with the Perjeta regimen also
were 40% less likely to experience disease recurrence
or death (DFS HR=0.60; 95% CI, 0.28–1.27).
The results suggested that people who achieved
pathological complete response (pCR; no tumor
tissue detectable at the time of surgery in the affected
breast and local lymph nodes) were more
likely across all arms of the study to be alive and
disease-free at three years (PFS HR=0.54; 95% CI,
0.29–1.00; DFS HR=0.68; 95% CI, 0.36–1.26). It
previously was reported that the Perjeta regimen
significantly increased the number of people
who achieved pCR compared to Herceptin and
docetaxel chemotherapy (39.3% v. 21.5%). In
2013, the FDA granted accelerated approval of
the Perjeta regimen for neoadjuvant treatment
in people with high-risk, HER2-positive eBC.
Roche recently submitted a MAA to the EMA for
the Perjeta regimen as a neoadjuvant treatment
for people with HER2-positive eBC.
August 4, 2014
Celsion released result of an ongoing, open-label
phase II trial of ThermoDox in recurrent
chest wall breast cancer (RCWBC). The trial is
designed to enroll 20 patients at several U.S.
clinical sites and is evaluating ThermoDox in
combination with mild hyperthermia. Of the 13
patients enrolled and treated, 10 were eligible
for evaluation of efficacy. To date, 60% of patients
experienced a stabilization of their highly
refractory disease with a local response rate
of 50% observed in the 10 evaluable patients,
notably three complete responses, two partial
responses and one patient with stable disease.
April 14, 2014
Synta Pharmaceuticals issued interim
results from a single-arm, multi-center, phase
II proof-of-concept study designed to evaluate
ganetespib for the treatment of metastatic
breast cancer. Target enrollment is 35 patients
in three cohorts, which include HER2+ breast
cancer, triple-negative breast cancer (TNBC)
and, recently added and now recruiting,
ER/PR-positive patients previously untreated
for locally advanced or metastatic disease.
The goal of the trial design is to obtain initial
evidence of a clinical activity signal with
single-agent ganetespib administered for
up to 12 weeks. Ten patients were enrolled
into the HER2+ cohort and 38 patients were
enrolled into the TNBC cohort. Of the patients
evaluable for metabolic response based on
having reached the week 3 PET assessment,
six of seven achieved a metabolic response
in the HER2+ cohort and 18 of 31 achieved
a metabolic response in the TNBC cohort.
Of the 6 HER2+ and 26 TNBC patients that
reached the six-week assessment and therefore
evaluable for objective RECIST response, four
achieved an objective response and two
achieved stable disease in the HER2+ cohort,
while two achieved an objective response, 11
achieved stable disease and 13 had progressive
disease in the TNBC cohort. One HER2+ patient
achieved a complete objective response and
has remained on treatment for over 10 months.
February 10, 2014
Pfizer issued results of a phase II trial of
palbociclib for the treatment of human
epidermal growth factor receptor 2 negative
(HER2-) locally advanced or newly diagnosed
metastatic breast cancer. The phase
II, multi-center trial, with 101 global sites
participating, was designed to assess the
PFS of palbociclib (125mg once daily for
three out of four weeks in repeated cycles)
in combination with letrozole v. letrozole
alone (2.5mg once daily on a continuous
regimen) in post-menopausal women with
ER+, HER2- advanced breast cancer. PFS is
comprised of time from randomization to
time of disease progression or death from
any cause. A randomized, global phase III
trial (PALOMA-2) in this patient population is
currently enrolling patients.
November 18, 2013
Angiochem released results of a phase II
study of ANG1005 in 80 HER2-positive and
HER2-negative breast cancer patients with
brain metastases. Two doses, 650mg/m2
(n=13) and 550mg/m2 (n=67), were evaluated
for intracranial anti-tumor responses
including response rate, progression-free survival
(PFS) and overall survival (OS). ANG1005
adverse events included neutropenia,
fatigue, peripheral neuropathy and mucosal
inflammation. HER2-positive patients (n=36)
achieved PR’s (9, 25%) and stable disease
(SD) (18, 50%) thereby demonstrating
disease control in 75% of those patients. At
550mg/m2, three month PFS was 71% with a
median PFS of 128 days and OS at six months
of 82%. Her2-negative patients (n=44)
achieved PR’s (5, 11%) and SD (17, 32%),
demonstrating disease control in 50% of
patients. In addition, at 550mg/m2, three
months of PFS was 35% with a median PFS
of 84 days and OS at six months of 60%.
Angiochem will advance ANG1005 into a
phase II clinical study in patients with
recurrent high grade gliomas and a phase II
clinical study in HER2-positive breast cancer
patients with brain metastases.
June 10, 2013
Novartis reported results from a phase III trial of Afinitor for the treatment of HER2 positive advanced breast cancer. This randomized, double-blind study of everolimus plus trastuzumab and vinorelbine conducted at 159 clinical trial sites globally included 569 women with HER2 positive locally advanced or metastatic breast cancer who were previously treated with a taxane and were resistant to trastuzumab. Subjects received either everolimus 5mg/day orally or placebo, plus weekly vinorelbine 25mg/m IV and weekly trastuzumab 2mg/kg IV following a loading dose of 4mg/kg. The primary endpoint of significantly extended progression-free survival (PFS) when compared to treatment with placebo plus trastuzumab and vinorelbine was met. Final PFS results showed adding everolimus to the standard treatment of trastuzumab and vinorelbine reduced the risk of disease progression by 22% (hazard ratio=0.78 [95% confidence interval (CI):0.65 to 0.95]; p<0.01). Median time to progression was 7.0 months in the everolimus combination arm and 5.8 months in the placebo combination arm. Adverse events were consistent with the known safety profile of everolimus. The most common all-grade adverse reactions (incidence >30%) were neutropenia, stomatitis, anemia, leukopenia, fatigue, pyrexia, diarrhea, nausea, decreased appetite and constipation.
May 20, 2013
Syndax Pharmaceuticals published results from a phase II trial of entinostat for the treatment of estrogen receptor-positive (ER+) breast cancer in the Journal of Clinical Oncology. This randomized, double-blind, placebo-controlled study, ENCORE 301, enrolled 130 postmenopausal women with ER+ breast cancer whose cancer had progressed after treatment with a nonsteroidal aromatase inhibitor. Subjects received 25mg exemestane daily plus 5mg entinostat once per week, or 25mg exemestane plus placebo. Based on intent-to-treat analysis, patients treated with entinostat saw improved median progression-free survival to 4.3 months versus 2.3 months in patients treated with placebo (hazard ratio 0.73; 95% confidence interval, 0.50 to 1.07; one-sided p=.055; two-sided p=.11). Overall survival was an exploratory endpoint, and median survival improved to 28.1 months in entinostat-treated patients versus 19.8 months in placebo-treated (hazard ratio 0.59; 95% confidence interval, 0.36 to 0.97; p=.036). Entinostat was well tolerated. The most frequent adverse events were fatigue and neutropenia. Based on this data, Syndax Pharmaceuticals is working to move entinostat into a confirmatory pivotal study this fall.
June 4, 2012
Celldex Therapeutics reported preliminary results from a phase IIb trial of CDX-011 (glembatumumab vedotin) as a conjugate for the treatment of advanced, refractory breast cancers with high glycoprotein NMB (GPNMB) expression. The randomized, multi-arm study, EMERGE, enrolled 122 subjects whose tissue had at least 5% of cells expressing GPNMB. Subjects were divided into three arms. Subjects in the CDX-011 arm received a median of six prior courses of therapy, and patients on the IC arm received a median of five prior courses of therapy. Preliminary results suggest that CDX-011 induces impressive response rates compared to current available therapies, with a 32% overall response rate (ORR) thus far. Treatment in the IC chemotherapy arm resulted in only a 13% ORR. In patients with both triple negative breast cancer and high GPNMB expression, a statistically significant progression-free survival benefit in the CDX-011 arm is currently observed (36% ORR) compared to the IC arm (0% ORR) (p&equiz;0.0032). The most common adverse events included rash and peripheral neuropathy. Based on these data, Celldex will continue the phase IIb study, with final results available in Q4 2012.
October 3, 2011
Novartis released results from a phase III trial of Afinitor for breast cancer. This randomized, double-blind, placebo-controlled trial, BOLERO-2, enrolled 724 postmenopausal female subjects with ER+HER2- advanced breast cancer. The subjects received either everolimus 10 mg/day orally or placebo, both added to oral exemestane 25 mg/day. The trial met its primary endpoint of progression free survival (PFS), showing treatment with everolimus improved PFS to 6.9 months compared to 2.8 months (p<0.0001) and significantly reduced the risk of cancer progression by 57% versus exemestane alone.
September 12, 2011
Syndax issued results from a phase II trial of entinostat for the treatment of breast cancer. This multicenter, randomized, double-blind, placebo-controlled trial, ENCORE-301, enrolled 130 postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer. The subjects received exemestane (Aromasin) 25mg daily plus entinostat 5mg orally once per week or exemestane plus placebo orally once per week. The primary endpoint was progression free survival. In the intent-to-treat population progression-free survival was significantly longer with exemestane plus entinostat than with exemestane plus placebo (4.28 versus 2.27 months, respectively; p≡0.06). In the intent-to-treat population, with a median follow-up of 18 months, overall survival was also significantly longer with exemestane plus entinostat than with exemestane plus placebo (26.94 versus 20.33 months, respectively; p≡0.027). Entinostat combined with exemestane was well tolerated.
July 11, 2011
Novartis reported positive interim results from a phase III trial of everolimus for the treatment of ER+HER2- metastatic breast cancer. This randomized, double-blind, placebo-controlled trial, BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) enrolled approximately 705 postmenopausal women refractory to the nonsteroidal aromatase inhibitors letrozole or anastrozole. The subjects received everolimus 10 mg daily in combination with exemestane 25 mg daily or placebo plus exemestane. Interim results showed everolimus plus exemestane significantly extended progression free survival compared to placebo plus exemestane. Based on these results the trial was stopped early.
December 20, 2010
Nektar Therapeutics reported results from a phase II trial of NKTR-102 for metastatic breast cancer. This two-stage design study enrolled 70 women who had failed a prior taxane therapy. Two dose regimens of single-agent NKTR-102 (145 mg/m2) were under evaluation; every 14 days (q14) and every 21 days (q21). Data are from 66 evaluable subjects. The confirmed overall response rate (ORR) was 32% for the q14d schedule and 26% for the q21d schedule, including two confirmed complete responses (CRs) on the q14d schedule. An additional four subjects had near CRs, with 100% disappearance of all target lesions. The combined ORR for all evaluable patients was 29%. The clinical benefit rate for the 66 evaluable patients was 41% (defined as CR+PR+SD greater than or equal to 6 mos). The confirmed ORR was maintained in poor prognosis and heavily pre-treated subsets within the study. The preliminary median progression-free survival for all subjects was 20 weeks.
October 11, 2010
Array Biopharma issued positive interim results from a phase I trial evaluating ARRY-380 for HER2 positive metastatic breast cancer. Data are from 17 subjects who were treated with ARRY-380 at doses greater than or equal to 200 mg twice daily. All of these subjects had been previously treated with Herceptin and the majority were previously treated with Tykerb. Of the 17 subjects, 29% had a partial response or stable disease for six months or longer and 13 had measurable disease as defined by RECIST; of these 13 patients, seven (54%) had regressions in target lesions. Of the four patients with no measurable disease, three had regressions of non-target chest wall lesions as documented by photographic evaluation. The maximum tolerated dose was established as 600 mg twice daily.
July 19, 2010
Novelos released positive results from a phase II trial of NOV-002 for breast cancer. This open-label, single-arm, Simon 2-Stage trial was designed to determine if preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel (AC-T) results in at least a doubling in the rate of pathologic complete response (pCR) compared to a historical control. In order to reach the primary endpoint, a minimum of 12 subjects must achieve a pCR. To date, 39 subjects with stage IIB-IIIC HER-2/neu negative invasive breast cancer have been enrolled. There were 12 confirmed pathologic complete responses out of 31 subjects (39%) who have undergone surgery. The historical response rate in this population is in the range of 10-20%. In addition, high pCR rates were observed in the breast cancer subtype least sensitive to chemotherapy, hormone receptor positive breast cancer. Confirmed pCR was reported in approximately 11 of 26 (42%) of this subpopulation.
June 14, 2010
Geron issued positive interim results from a phase I/II trial of imetelstat for the treatment of breast cancer. This open label, dose escalation study had enrolled 14 subjects with locally recurrent or metastatic breast cancer. The subjects received imetelstat by two hour intravenous infusions on days one, eight and 15 of 28 day treatment cycles. Dosing started at 160 mg/m2 and escalation proceeded to 375 mg/m2. The subjects also received a chemotherapy combination regimen of 90 mg/m2 paclitaxel (Taxol) on days one, eight and 15, and 10 mg/kg bevacizumab (Avastin) on days one and 15, both by intravenous infusion. The preliminary confirmed overall response rate was 53.8% and the median duration of response was 21.7 weeks. Infusions of imetelstat were generally well tolerated and acute dose limiting toxicities were not observed.
June 7, 2010
Peregrine Pharmaceuticals released positive results from a phase II trial of bavituximab for the treatment of breast cancer. This open label trial, based in India, enrolled 46 female subjects with locally advanced or metastatic breast cancer. The subjects received weekly bavituximab (3 mg/kg ) carboplatin (AUC≡2 ) and paclitaxel (100 mg/m2) on days 1, 8, and 15 of a 28-day cycle for up to 6 cycles. The primary endpoint was to determine overall response rates for the combination treatment. By the end of the treatment period, 74% of the subjects achieved an objective tumor response and 9% achieved a clinical complete response. The median progression free survival was 6.9 months.
May 17, 2010
MediGene AG reported positive preliminary results from a phase II trial of EndoTAG-1 for the treatment of triple receptor negative breast cancer. This trial enrolled 140 women who were randomized to one of three treatment groups: EndoTAG-1 monotherapy (44 mg/m2 twice per week), EndoTAG-1 (22 mg/m2 once a week) in combination with paclitaxel (70 mg/m2) or paclitaxel alone (90 mg/m2 once per week). The primary endpoint was progression free survival at 16 weeks of at least 30% in both EndoTAG treatment groups. The EndoTAG-1 and paclitaxel combination group showed a progression-free survival rate of 59.1%. The progression-free survival rate of the EndoTAG- 1 monotherapy was 34.2% and in the paclitaxel monotherapy group the progression-free survival rate was 48%.
September 28, 2009
Bayer and Onyx released positive results from a phase II trial of Nexavar in combination with capecitabine for the treatment of breast cancer. This randomized, double-blind, placebo-controlled study enrolled 229 female subjects with locally advanced or metastatic HER-2 negative breast cancer who had received no more than one prior chemotherapy. The subjects received 400 mg of oral Nexavar or matching placebo twice daily, both in addition to 1000 mg/m(2) of capecitabine twice daily for 14 days, followed by a seven day rest from capecitabine. The primary endpoint, progression-free survival, was reached with statistical significance. The Nexavar plus capecitabine arm showed a 74% improvement over capecitabine alone. The difference in median progression-free survival of Nexavar plus capecitabine versus capecitabine plus placebo was 6.4 months versus 4.1 months (p≡0.0006).
August 3, 2009
Ariad reported results from two trials of ridaforolimus for the treatment of breast cancer and solid tumors. The first was a phase II study of ridaforolimus combined with trastuzumab for metastatic breast cancer. This ongoing trial has enrolled 28 subjects with metastatic breast cancer who have become resistant to trastuzumab. The subjects received oral ridaforolimus (40 mg/day, once daily) and trastuzumab at standard doses and intervals. The primary endpoint was objective response rate defined by RECIST criteria in at least 15% of the population. Of 28 refractory patients enrolled thus far, 15 currently remain on study without disease progression. At least five partial responses have been observed to date and the preliminary clinical benefit rate was 35%. The second trial was a phase I trial of ridaforolimus combined with bevacizumab in solid tumors. This study enrolled 17 subjects with metastatic solid tumors who had become resistant to bevacizumab. The subjects received the standard dose of oral ridaforolimus (40 mg/day, qdx5) in combination with each of the two approved bevacizumab dosing regimens (infusions every two or three weeks). Of the 17 enrolled subjects, 5 remain on study without disease progression. To date, the longest duration of stable disease was 10 cycles of therapy in a patient with advanced pancreatic cancer; this patient also had a 13% reduction in tumor size.
July 13, 2009
Amgen released positive results from a phase III trial of denosumab for the treatment of bone metastases due to breast cancer. This international, randomized, double-blind study enrolled 2,049 female subjects with advanced breast cancer and bone metastases. The subjects were randomized to receive either 120 mg of denosumab subcutaneously every four weeks (Q4W) or Zometa administered intravenously at a dose of 4 mg single, 15 minute infusions every four weeks. The primary endpoint was to evaluate if denosumab is non-inferior to Zometa with respect to the first on-study Skeletal Related Events (SREs). Superiority was demonstrated with statistical significance for both delaying the time to the first on-study SREs (fracture, radiation to bone, surgery to bone, or spinal cord compression) and delaying the time to the first-and-subsequent SREs. There were no unexpected adverse events or serious adverse events. Overall survival and the time to cancer progression were similar between the treatment arms.
June 8, 2009
Sanofi-Aventis and BiPar Sciences issued positive results from a phase II trial of BSI-201 for the treatment of breast cancer. This multicenter, randomized, open-label study enrolled 116 female subjects with metastatic triple-negative breast cancer (TNBC). The subjects received gemcitabine and carboplatin (GC) in combination with BSI-201 or GC alone. The primary endpoint was the rate of clinical benefit, defined a partial or complete response or stable disease of at least six months. Approximately 62% of subjects receiving BSI-201 in combination with GC showed clinical benefit, compared with 21% of subjects receiving chemotherapy alone (p≡0.0002). Tumor response (complete or partial) was observed in 48% of the GC/BSI-201 arm compared to a response rate of 16% in the GC alone arm. The subjects who received BSI-201 had a median progression-free survival of 6.9 months and overall survival of 9.2 months compared with 3.3 and 5.7 months, respectively, for women who received chemotherapy alone (p<0.0001) and (p≡0.0005), respectively. The combination treatment was generally well tolerated.
March 2, 2009
Bavarian Nordic reported positive results from two phase I/II trials of MVA-BN-HER2, a vaccine for the treatment of breast cancer. The first study took place in the United States and evaluated MVA-BN-HER2 treatment following chemotherapy and Herceptin. The second study took place in Serbia and Poland and investigated MVA-BN-HER2 following only chemotherapy or in combination with single-agent taxane chemotherapy. A total of 30 subjects were enrolled. They were vaccinated three times, at three week intervals. The primary endpoints, safety and efficacy, were both reached. Evidence of vaccine-induced anti-HER2 immune response was detected in approximately 70% of the evaluated subjects. At six months, disease progression was avoided in 15 of 30 subjects. In addition, in the group where MVA-BN-HER-2 was combined with taxane chemotherapy, one complete response and one partial response were observed. No drug-related severe adverse events were reported and the vaccine was well tolerated.
February 16, 2009
Novartis, in conjunction with the Austrian Breast & Colorectal Cancer Study Group, released positive results from a phase III trial of Zometa for the prevention of recurrent early breast cancer. This open label, multi-center study, dubbed ABCSG-12, enrolled 1,803 premenopausal women with estrogen receptor-positive Stage I or II breast cancer, with fewer than 10 axillary lymph nodes involved. Following curative surgery and goserelin treatment to suppress the ovaries, the subjects were randomized to one of four study groups: anastrozole plus Zometa; anastrozole alone; tamoxifen plus Zometa or tamoxifen alone. The treatment duration was three years. The primary endpoint was disease-free survival and the secondary endpoints included recurrence-free survival and overall survival. At the median follow-up of 48 months, disease-free survival was reduced by 36% (P≡0.01) and the risk of recurrence-free survival events fell by 35% (p≡0.02) when Zometa was added to hormone therapy versus hormone therapy alone. While not statistically significant, a positive trend was observed for overall survival (p≡0.11) and bone metastasis-free survival (p≡0.22) in the Zometa plus hormone therapy arms compared to the hormone therapy alone arms. Treatment was generally well-tolerated and there were no unexpected adverse events.
Sopherion reported positive results from a phase I/II trial of Myocet in combination with Herceptin (trastuzumab) plus Taxol (paclitaxel) for the treatment of breast cancer. This multi-center, open label study enrolled 69 subjects with HER-2-overexpressing locally advanced non-operable breast cancer or metastatic breast cancer, in Spain. The subjects received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and Myocet every three weeks for six cycles. The primary endpoint was overall response rate, defined as the total of complete response plus partial response. Left ventricular ejection fraction (LVEF) was monitored every three weeks for the first 18 weeks and every eight weeks thereafter. The overall response rate was 98.1%; complete response was achieved by 29 subjects (53.7%) and 24 subjects (44.4%) had a partial response. The median time to progression was not reached in patients with locally advanced nonoperable breast cancer, while it exceeded 21 months in those with metastatic breast cancer. The combination therapy was well-tolerated and there were no reports of symptomatic treatment-related cardiac failure.
October 6, 2008
Apthera reported results from a phase I/II study of NeuVax for the treatment of breast cancer. This dose escalation trial enrolled 99 subjects and was designed to determine the optimal dosing for phase III studies. The subjects were treated with either a low dose or high dose of Neuvax in combination with Leukine (GM-CSF), or standard of care. The subjects who received the high dose regimen had significantly worse prognostic factors prior to treatment compared to subjects given lower doses, including larger tumors and more positive lymph nodes. At a median follow-up of 30 months, the tumor recurrence rate for subjects receiving the higher dose of NeuVax was much lower than that of subjects receiving suboptimal doses (3.4% versus 12.9%). The group who received standard of care experienced a recurrence rate of 14.8% at 30 months. Based on the results, the optimal dose and schedule of NeuVax for phase III trials was established as NeuVax 1 mg combined with Leukine (GM-CSF) 250 mg via monthly intradermal administration for six months. Phase III trials are expected to commence shortly.
July 28, 2008
Peregrine released positive interim results from an ongoing phase II trial of bavituximab for the treatment of breast cancer. To date, 15 subjects with metastatic breast cancer had been enrolled in the first stage of this open label, Simon two-stage design study and had received a combination of bavituximab and docetaxel. The Stage 1 primary endpoint was six or more objective tumor responses. Fourteen of the 15 subjects were deemed evaluable for tumor response. Seven achieved partial tumor responses and seven had stable disease at week eight according to RECIST criteria. All 14 of the evaluable subjects were continuing to receive treatment, along with continuing assessments of tumor response. Based on the positive results seen in the first stage, an additional 31 subjects will be enrolled in Stage 2 of the study.
June 16, 2008
Bayer Schering reported positive results from a phase II trial of Leukine for the treatment of melanoma. This 24-month, single-arm, open-label study enrolled 45 subjects who had undergone potentially curative surgery. In the first year of treatment, Leukine was administered subcutaneously at 125mcg/m2/day for 14 consecutive days, followed by Interleukin-2 (IL-2) subcutaneously at nine million IU/m2/day for four days. The subjects then received no treatment for ten days. In the second year of treatment, Leukine was administered alone two times per week. In the subjects who experienced resected recurrence, the same adjuvant therapy was re-administered. At the end of the study, 32 of the original 45 subjects were alive. The survival data, expressed by Kaplan- Meier, showed disease-free survival of 60% and overall survival of 64% at 21 months. There was no statistical difference in survival by Log Rank between those who received only Leukine versus those treated by Leukine and IL-2 (p=.8). In addition, there was no increase in the number of dendritic cells during or after Leukine administration in 11 subjects who donated blood for dendritic cell counts. Leukine was generally well-tolerated, with toxicities mild to moderate in nature. Based on the results Bayer plans to move forward with the development of Leukine for this indication.
Epeius reported positive results from an ongoing phase I/II trial of Rexin-G for the treatment of breast cancer. This US, open-label, dose-comparison enrolled 24 subjects with rapidly progressive chemotherapy resistant breast cancer. The subjects received dose-escalations of Rexin-G given intravenously two to three times a week for four weeks, with doses ranging from 2 x 10e11 cfu to 6 x 10e11 cfu per week. The goal of the adaptive trial design was to confirm the over-all safety of Rexin-G and to determine the optimal dosing regimen. Rexin-G demonstrated significant biological activity without toxicity. Escalating doses of Rexin-G were associated with stabilization of disease, significant reductions in CA 15.3 levels, a median progression-free survival of six months and a median over-all survival of greater than seven months, with all subjects surviving at the 8-month follow-up period. Rexin-G was safe and well-tolerated up to the highest tested dose. Based on the results Epeius plans to continue with the trial as planned.
Gloucester released positive results from a phase IIb trial of romidepsin for the treatment of cutaneous T-cell lymphoma (CTCL). This non-randomized, open-label, single-arm international study, dubbed GPI-04-0001, enrolled 96 subjects. The subjects received romidepsin at a dose of 14 mg/m(2) intravenously on days 1, 8 and 15 of each 28-day cycle, for 6 cycles. Data is from 72 evaluable subjects. The primary endpoint, overall response rate, was achieved. In subjects who had failed previous therapy, 40.3% reached this goal. Partial response was observed in 33.3% and 6.9% of subjects achieved a complete response. The overall response rate in subjects with advanced stage disease was 47.9%, with 37.5% experiencing a partial response and 10.4% experiencing a complete response. Additionally, 92.3% of subjects with pruritus at the outset of the trial had some relief. Gloucester plans to file an NDA with the FDA later in 2008.
December 3, 2007
Cytos issued positive preliminary results from three phase IIa trials of CYT004 -MelQbG10, a vaccine for the treatment of melanoma. These parallel open-label studies enrolled twenty-two subjects with various stages of malignant melanoma. The trial was designed to assess safety, tolerability and T cell immunogenicity of three different dose regimens of CYT004-MelQbG10 as well as to compare two different routes of administration. All doses of the vaccine were safe and well tolerated, with no reported serious adverse events. Upon vaccination, Melan-A (MART-1)-specific CD8+ T cell responses could be detected directly ex vivo in fourteen of twenty-two subjects, indicating a good T cell immunogenicity. In the subjects who responded to the vaccine, the melanoma-specific CD8+ T cells increased by a median factor of three (individual increases were two to eight fold). Seven of the twenty-two subjects entered the study without detectable tumor after surgical intervention. Of these seven, six subjects remained tumor free throughout the treatment period. Fifteen subjects entered the study with detectable metastases. Of these fifteen, eleven subjects had progressive disease leading to death of two; one subject had stable disease, one subject showed partial response, one subject was not assessable because the tumor lesion was removed during the trial, and one subject died before the final assessment. Based on the results Cytos plans to move forward with the development of CYT004-MelQbG10, with additional trials planned for 2008.
Immutep reported positive interim results from a phase I/II trial of ImmuFact IMP321 for the treatment of metastatic breast cancer. This open-label, fixed dose-escalation study was designed to evaluate standard doses of weekly paclitaxel in combination with two IMP321 doses, 0.25 and 1.25 mg given subcutaneously at day two and day sixteen of a four-week cycle, for six courses. Data are from the first cohort of eight subjects who received the 0.25 mg dose of IMP321. Treatment was well tolerated. Out of the eight subjects, there were six tumor regressions and one disease stabilization. A three-fold increase in activated MHC class II+ monocyte blood counts and a two-fold increase in activated CD8+ circulating T cells were observed two weeks after the last injection. This trial is ongoing at the Ren Huguenin Cancer Centre, Saint Cloud in France.
September 24, 2007
Exelexis announced positive interim results from a phase II trial of XL647 for the treatment of non-small cell lung cancer (NSCLC). Reported data is from 30 evaluable subjects with stage IIIB or IV NSCLC who received XL647 administered orally, at a dose of 350 mg on days 1-5 of repeated 14-day cycles. To date 8 partial responses and 11 stable disease had been reported. Of the 8 subjects who experienced partial responses, 4 had epidermal growth factor receptor (EGFR) exon 19 deletions, 1 had an EGFR L858R mutation, and 3 were EGFR wild-type. All 6 subjects with EGFR-activating mutations demonstrated clinical benefit, with 5 partial response and 1 stable disease. Treatment was generally well tolerated. Additional phase II trials are currently underway.
Kosan issued positive results from a phase I trial of alvespimycin for the treatment of breast and ovarian cancer. This trial enrolled 25 subjects who received one-hour weekly intravenous infusion of 60, 80 or 100 mg/m2 alvespimycin administered along with the standard dose of trastuzumab. The subjects were assessed every four weeks for toxicity and every eight weeks for response, as measured by RECIST criteria and tumor markers. Clinical benefit was observed in 42% of evaluable subjects with HER2-positive metastatic breast cancer. This included one subject with complete resolution of lung metastases, one subject with a 10% reduction in tumor mass and tumor necrosis, one subject with a partial response after 2 cycles and five subjects with stable disease. Of the subjects with ovarian cancer, there was one subject with a near complete resolution of ascites and left pleural effusion at the end of cycle 2. Based on the results, Kosan plans to expand the phase I trial to add weekly dosing with paclitaxel. Phase II trials are planned for Q4 of 2007.
Merck reported positive long-term results from a phase II trial of Stimuvax for the treatment of non-small cell lung cancer (NSCLC). This study enrolled 171 subjects with stage IIIB/IV nsclc with stable or responding disease after any first-line chemotherapy with or without radiotherapy. The subjects were stratified by disease stage than randomized to receive Stimuvax plus best supportive care (BSC) or BSC alone. The subjects in the Stimuvax arm received a single intravenous dose of cyclophosphamide 300mg/m2 followed by 8 weekly subcutaneous immunizations with Stimuvax (1,000 mg). Although the overall study results did not reach statistical significance, the subjects with stage IIIB cancer receiving Stimuvax showed a median survival of 30.6 months versus 13.3 months in the control group. At the three year follow-up, 49% of the subjects who were treated with Stimuvax were still alive versus 27% treated with BSC alone, representing a 45% reduction in mortality. Based on the results, Merck is currently conducting a phase III trial of Stimuvax for the treatment of stage IIIA or IIIB non-small cell lung cancer.
Pfizer released positive preliminary results from a phase II trial of sunitinib for the treatment of non-small cell lung cancer (NSCLC). The trial was designed to compare sunitinib (37.5 mg/day) in combination with erlotinib (150 mg/day) in previously treated subjects with advanced NSCLC. The primary endpoint was safety and tolerability. Secondary endpoints included anti-tumor activity. The combination treatment was generally safe and well tolerated, with all adverse events mild to moderate in nature. Two subjects had partial response; one which was maintained for >3 months and one which was currently ongoing. In addition, stable disease up to or more than 16 weeks was observed in two subjects. The randomized portion of this trial is currently underway.
YM BioSciences announced positive preliminary results from a phase I/II trial of nimotuzumab for the treatment of non-small cell lung cancer (nsclc). This trial had enrolled 13 subjects to date in Canada. The subjects received nimotuzumab at three dose levels (100 mg, 200 mg and 400 mg weekly) with palliative radiation. Of the six subjects enrolled in the first cohort (100 mg), four partial response (PR) and two stable disease (SD) were reported. Median Overall Survival was 41.5 weeks. Of the seven subjects in the second cohort (200 mg) two PR and five SD were reported. Median Overall Survival in this group had not been reached but exceeded 25 weeks at this time. Treatment was generally well tolerated in both arms. Enrollment in the third cohort is underway, with accrual anticipated to be completed by the end of 2007. These results will be used to determine the optimal dose for the randomized phase II portion of the study.
September 17, 2007
Ardana announced positive preliminary results from a phase II trial of teverelix for the treatment of prostate cancer. This 8-week randomized trial enrolled 38 subjects who received either low dose or high dose teverelix. The primary endpoint was duration of testosterone suppression to below castration level (< 0.5 ng/ml). Secondary endpoints included the percentage of subjects attaining and maintaining medical castration, an evaluation of prostate specific antigen (PSA) and luteinizing hormone levels, and local and systemic tolerability of the drug. By day three, testosterone suppression was attained in 14 and 18 subjects in the low- and high-dose groups, respectively. A total of 19 high-dose-treated subjects had a reduction of testosterone levels to castration level, the duration of which was between 54 to 147 days, with 17 subjects being castrated for 8 weeks or more. In addition, at week 4 normalized PSA (< 4.0 ng/ml) levels were observed in 74% of the high dose group and mean PSA levels were normalized at 8 weeks. Based on the results, Ardana plans to advance the development of teverelix.
AstraZeneca released positive results from a phase III trial of Iressa for the treatment of non-small cell lung cancer (nsclc). This trial was dubbed INTEREST (IRESSA Non-small-cell lung cancer Trial Evaluating REsponse and Survival against Taxotere) and enrolled 1,446 subjects with pre-treated nsclc. The trial was designed to compare the overall survival of subjects treated with oral Iressa to intravenous docetaxel. The results established non-inferiority between Iressa and docetaxel. In addition, Iressa demonstrated a more favorable tolerability profile and superior quality of life for subjects versus docetaxel. Iressa has been approved for the treatment of nsclc in several international markets.
EntreMed issued positive interim results from a phase II trial of MKC-1 for the treatment of metastatic breast cancer. This single agent trial enrolled 40 subjects with metastatic breast cancer who had failed therapy with anthracyclines and taxanes. The subjects received orally administered MKC-1 (125 mg/m2) twice-daily on a 28 day dosing schedule. Of 35 evaluable subjects there was one complete response, two partial responses and three stable diseases of greater than four months. Based on the results the second stage of this trial has commenced and is enrolling an additional 53 subjects to assess objective response rates.
August 27, 2007
Dendreon announced positive results from a phase I trial of Neuvenge for the treatment of breast cancer. The trial enrolled 18 subjects with HER2-overexpressing metastatic breast cancer who had failed standard therapy. The subjects were randomized to receive three infusions of Neuvenge at weeks 0, 2, and 4. Those who achieved a partial response, or had stable disease lasting through week 52, were eligible for re-treatment, a booster, using the same protocol and dose as the initial treatment. Treatment was generally well tolerated, with all adverse events mild to moderate in nature. Neuvenge stimulated significant immune responses, which were shown to be enhanced following booster infusions. Anti-cancer activity was observed in 22% of the subjects, including one partial response lasting approximately 6 months and three subjects with stable disease for over a year. Based on the results, Dendreon plans to continue with the development of Neuvenge.
June 25, 2007
Allos released negative top-line results from a phase III trial of Efaproxyn for the treatment of women with brain metastases as a result of breast cancer. This randomized, open-label study, called ENRICH (ENhancing Whole Brain Radiation Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases), enrolled 368 subjects internationally. It was designed to compare the effect of whole brain radiation therapy (WBRT) with supplemental oxygen with or without Efaproxyn in treating this population. The trial failed to meet the primary endpoint of demonstrating a statistically significant improvement in overall survival between the two arms. The subjects who received Efaproxyn plus WBRT had an overall survival of 8.5 months while those who received WBRT alone had an overall survival of 7.5 months (hazard ratio 0.87, p-value = 0.23). All secondary endpoints also failed to reach statistical significance. Based on the results, Allos will discontinue the development of Efaproxyn and focus on the development of other therapies in the pipeline.
Neoprobe issued positive preliminary results from a phase II trial of Lymphoseek for the detection of breast cancer or melanoma in lymph nodes. This multicenter, single-arm, open-label, within-patient, single-dose, multi-stage trial enrolled 40 women in the US. The primary endpoint was to measure the rate at which Lymphoseek localized to lymphoid tissue with a goal of achieving 90% localization. This endpoint was achieved in over 94% of the Sentinel Lymph Node Biopsy (SLNB) procedures performed. Based on the results, Neoprobe is preparing to submit a pivotal trial protocol to the FDA.
February 5, 2007
Cell Genesys announced positive long-term data from a phase II trial of GVAX for the treatment of operable pancreatic cancer. This trial enrolled 60 subjects who received GVAX after surgical resection of their tumor and adjuvant radiation and chemotherapy. GVAX was administered intradermally before and after standard post-operative adjuvant radiation therapy and 5-flourouracil chemotherapy. Treatment was administered at up to five doses, the first prior to adjuvant chemoradiotherapy, the next three following adjuvant therapy at approximately one-month intervals and the fifth as a booster injection six months later. Treatment was well tolerated through the study duration. The long-term survival results revealed a median survival of 26.8 months. GVAX is currently in phase III trials for the treatment of pancreatic cancer.
Sunesis reported interim results from two phase II trials of SNS-595 for the treatment of small cell lung cancer and non-small cell lung cancer. Both trials employed a two-stage design with an interim assessment between each stage. Objective response rate, as defined by RECIST (Response Evaluation Criteria in Solid Tumors) was the determination for advancing to stage two. All subjects received SNS-595 at the MTD of 48 mg/m2 every three weeks. The small cell cancer trial included a treatment-sensitive arm and a treatment-refractory arm. Nine out of eleven evaluable subjects in the treatment-sensitive arm had stable disease or objective response by the end of two cycles of treatment, which exceeded the pre-specified requirements for advancing to stage two. In the treatment-refractory arm, none of the 20 evaluable subjects reached objective response, although there were reports of stable disease. Based on the data, enrollment in this arm was discontinued. The non-small cell cancer trial enrolled 25 subjects who had previously failed first-line treatment. Although 50% had achieved stable disease or better, objective response rates were not observed. Based on these results, enrollment was discontinued in this trial. Sunesis plans to explore additional clinical evaluation of SNS-595 in combination with other anti-cancer agents in the treatment of non-small cell lung cancer pending the full evaluation of these results.
YM BioSciences released negative results from a phase III trial of tesmilifene combined with epirubicin/cyclophosphamide for the treatment of breast cancer. This trial, conducted under a Special Protocol Assessment by the FDA, enrolled 723 women with metastatic or recurrent breast cancer. Subjects received tesmilifene combined with epirubicin/cyclophosphamide or epirubicin/cyclophosphamide alone. A planned interim analysis was conducted to determine if there was a significant difference in overall survival rates between the two treatment groups, the primary endpoint. Review of the data found that such differences had not occurred and were unlikely to occur during the course of the trial. Based on this information, YM BioSciences terminated this trial.
January 15, 2007
Kosan issued positive preliminary results from a phase II trial of tanespimycin plus Herceptin for the treatment of Herceptin-refractory HER2-positive metastatic breast cancer. This trial was designed to determine the objective response rate according to RECIST criteria in subjects with HER2-positive metastatic breast cancer with tumor progression during treatment with one Herceptin-containing regimen immediately prior to entering the trial. The trial enrolled 12 subjects who received tanespimycin (450 mg/m2) via a two-hour weekly intravenous infusion administered along with the standard dose of Herceptin. Treatment was well tolerated, with adverse events mild in nature. Of the eight subjects evaluable for efficacy, five (63%) showed signs of clinical benefit and three who had received 4-6+ cycles of treatment had stable disease. Based on the results Kosan plans to advance the development of tanespimycin into phase III trials.
Vertex and Merck announced positive results from a phase I trial of VX-680 (MK-0457) for the treatment of resistant leukemias and myeloproliferative diseases. This trial enrolled 44 subjects with chronic myelogenous leukemia (CML), Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL), or myeloproliferative diseases (MPD). Subjects were treated with VX-680 given as a five-day intravenous infusion every two-to-three weeks. No treatment related toxicities were reported and thus the maximum tolerated dose was not yet determined. Out of the 15 subjects with CML, nine had a T315I BCR-ABL mutation. Eight of these nine T315I subjects had either a hematologic and/or cytogenetic response to VX-680 following multiple cycles of treatment. The six subjects without the T315I BCR-ABL mutation did not exhibit any clinical responses. In addition, two subjects in the study with Ph+ ALL carrying the T315I mutation had either hematologic and/or cytogenetic responses, including one who had a clinical response with a full molecular remission. Six of the nine subjects with MPD having the V617F activating mutation in JAK-2 also had clinical responses. Based on these results, a phase II trial is planned for January of 2007.
August 21, 2006
Pharmexa issued negative results from a phase II trial of PX104.1, in combination with QS-21, for the treatment of breast cancer. This trial planned to enroll 40 subjects who were to receive four initial immunizations of PX 104.1 (1.25mg), formulated with Alhydrogel adjuvant and mixed with QS-21 adjuvant, for six weeks, followed by booster immunizations every four weeks, for up to 26 weeks. Preliminary results from the first 10 vaccinated subjects demonstrated that this formulation failed to meet the trial's primary endpoint of objective tumor response. The vaccine did not slow down tumor growth and cancer progressed in all 10 subjects. Based on these results the trial was stopped. Pharmexa intended to analyze further data for possible expansion into a different patient population.
Raven Biotechnologies, Inc. reported positive preliminary results from a phase I trial of RAV12 for the treatment of adenocarcinomas. Data has been evaluated from three treatment cohorts of 21 subjects who received RAV12, intravenously, in weekly escalating doses of 0.3 mg/kg to 1.5 mg/kg, for over four weeks. Safety and tolerability outcomes established a maximum tolerated dose with associated side effects of infusion-associated abdominal discomfort and liver function test abnormalities. Abdominal discomfort and liver function test abnormalities were transient at lower dose levels. Preliminary efficacy data revealed that treatment with RAV12 led to one subject achieving partial remission and three subjects with stable disease. In two subjects time to disease progression surpassed four months. The phase I trial was ongoing at this time.
June 12, 2006
Ariad Pharmaceuticals announced positive results of a phase II trial of AP23573, for the treatment of soft-tissue and bone sarcomas. Trial data indicated significant improvements in the trial's co-primary endpoints, clinical benefit rate (CBR; combined rate of complete response, partial response and stable disease) and duration of progression-free survival (PFS) for patients with the three most common subclasses of sarcoma. Specifically, CBR was 30% for patients with bone sarcoma; 33% for leiomyosarcoma, and 30% for liposarcomas, compared to a historical baseline of 8%; rate of PFS through 6 months (24%) and median duration of PFS (15 weeks) did not significantly differ between the 3 groups, and was superior to a historical baseline of 7 weeks. Patients with less common "other" sarcomas experienced a 6-month PFS rate comparable to the other sub-groups, though CBR was lower (23%), and below the pre-determined 25% success threshold. This multi-center study enrolled 212 patients with metastatic and/or unresectable disease, who received fixed doses of 12.5 mg AP23573 monotherapy via intravenous infusion in 4-week cycles of 5 days on/9 days off treatment.
Exelixis reported positive results of a phase I trial of XL647, for the treatment of solid tumors. Trial data yielded preliminary evidence of efficacy, with 1 partial response (NSCLC) and 12 cases of stable disease through at least 3.5 months (3 NSCLC, 2 chordoma, 2 adenoid cystic carcinoma, and 1 each adrenocortical carcinoma, colorectal, ovarian, mesothelioma, and head & neck cancer). Maximum tolerated dose was set at 4.68 mg/kg; 2 subjects administered doses higher than this level experienced dose-limiting grade 3 diarrhea. This dose-escalation study enrolled 40 subjects, who were received multiple oral doses of the drug (0.06 mg/kg to 7.0 mg/kg).
GlaxoSmithKline reported positive results of a phase III trial, dubbed EGF100151, of Tykerb, for the treatment of breast cancer. Trial data yielded significant efficacy, significantly extending time to disease progression compared to control therapy (36.9 weeks vs. 19.7 weeks; p=0.00032). Rates of treatment-related adverse events leading to discontinuation were comparable between the Tykerb (14%) and control (11%) regimens. This international, multicenter, open-label study enrolled 392 women with trastuzumab-refractory ErbB2 positive breast cancer, who received either a combination regimen of Tykerb and the approved drug capecitabine, or capecitabine alone. These results were sufficiently positive for the trial's DSMB to recommend early termination of the study in April 2006, so all patients could be transferred to the combination regimen.
ImClone announced positive results of a phase I trial of IMC-1121B, for the treatment of advanced cancers. Maximum tolerated dose had yet to be reached, with anorexia, vomiting, anemia, depression, fatigue and insomnia noted as the most frequent adverse events. These adverse events were noted as potentially distinct from those observed with other compounds designed to disrupt the VEGF system. Preliminary evidence of efficacy was also noted, with 1 partial tumor response and 5 instances of stable disease. This open-label study had enrolled 14 subjects to date, and dose-escalation was ongoing.
Pharmion and MethylGene reported interim results of a pair of phase I trials of MGCD0103, for the treatment of hematological malignancies (leukemias and myelodysplastic syndromes (MDS)), and solid tumors. Both trials were open-label, dose-escalation monotherapy studies, which had enrolled 23 and 28 patients to date, respectively. In the leukemia/MDS study, the maximum tolerated dose was somewhat below 80 mg/m2 thrice weekly, at which dose nausea, vomiting, diarrhea, and/or fatigue were dose-limiting. 3 patients (2 with acute myelogenous leukemia, 1 with MDS) achieved complete bone-marrow response. In the solid tumor trial, maximum tolerated dose had not yet been reached; the most common adverse event to date was Grade 1-3 fatigue. Stable disease was observed in 5 subjects (3 kidney cancer, 1 NSCLC and 1 colon cancer). Based on these results, the company announced plans to initiate a phase I/II trial of the drug in Q2 2006, with phase II trials to follow before year's end.
December 12, 2005
Bionovo issued positive results of a phase I trial of BZL101, an extract of scutellaria barbata for the treatment of MBC. Safety data were generally positive, with no incidence of hematologic adverse events of any grade or serious (Grade 3/4) non-hematologic adverse events; overall adverse events included nausea (43%), diarrhea (20%), headache (20%) flatulence (14%), vomiting (10%), constipation (10%), and fatigue (10%). Preliminary safety data were also positive, with 25% of evaluable subjects (n=4/16) experiencing stable disease through at least 90 days, and 19% (n=3/19) experiencing stable disease through at least 180 days. Minor tumor responses were noted in 3 subjects. This open-label study enrolled 21 patients with confirmed, pretreated MBC (mean prior therapies =3.6), who received 350 ml BZL101 daily until evidence of disease progression, toxicity or decision to discontinue occurred.
Kosan and Roche announced positive interim results of a phase II trial of KOS-862, their recombinant polyketide microtubule stabilizer for the treatment of metastatic breast cancer (MBC). Trial data yielded evidence of efficacy, with 14% of patients (n=4) experiencing confirmed partial tumor response. This included two subjects with hepatic metastases whose tumor burden was reduced > 50%. One additional subject experienced an unconfirmed partial response. Grade 3 neurological toxicities were observed in 18.5% of subjects, including 3 cases of Grade 3 peripheral sensory neuropathy. This interim analysis evaluated 29 women with MBC previously refractory to anthracycline-plus-taxane chemotherapy. Enrollment and treatment of up to 53 subjects was ongoing.
Sonus Pharmaceuticals reported positive results of a phase IIb trial of TOCOSOL paclitaxel for the treatment of MBC. Efficacy data yielded a 48% confirmed partial response rate (n=22); an additional 9% of patients (n=4) experienced unconfirmed partial response, and 17% (n=8) experienced stable disease through 16 weeks. Median time to disease progression had yet to be reached. Safety data indicated that neutropenia was the most common overall (all-Grade) adverse event (87%) and serious (Grade 3/4) adverse event (66%). Additional adverse events included arthralgia/myalgia (34%) and infusion-related reactions (51%). Through 17 weeks, 20/47 subjects had discontinued treatment: 11 due to progressive disease, 7 due to toxicity and 2 due to other reasons. This open-label study enrolled 47 patients with previously untreated MBC, who received 120 mg/m2 TOCOSOL paclitaxel weekly for 16 weeks.
Taiho reported positive results of a phase I trial of TAS-108, for the treatment of hormone-responsive breast cancer. Preliminary safety data were generally positive, with 6 patients experiencing drug related Grade 1 toxicities, and 2 experiencing Grade 2. The most frequent adverse events were ALT abnormalities (n=3/15), hot flashes (n=2/15), and arthralgia (n=2/15). On patient experienced endometrial hypertrophy. Preliminary efficacy was noted: 2 patients experienced partial tumor response, and 3 experienced stable disease through 24 weeks, yielding a 13.3% objective response rate and a 33.3% clinical benefit. This open-label, single-ascending-dose study evaluated 15 post-menopausal Japanese patients with refractory disease, who received a starting dose of 40 mg TAS-108 daily; escalation to 80 mg and 120 mg was permitted if safety results were sufficiently positive.
June 6, 2005
Sanofi-Aventis reported positive results of a phase III trial of their approved taxane chemotherapeutic Taxotere (docetaxel), for the treatment of breast cancer, in the New England Journal of Medicine. Following surgical resection, administration of Taxotere produced significant improvements in 5-year disease-free survival rates (75% vs. 68%; p=0.001) and overall survival rates (87% vs. 81%; p=0.008) vs. treatment with 5-fluorouracil. Incidence of serious (Grade 3-4) adverse events was significantly higher with Taxotere, including neutropenia (65.5% vs. 49.3%; p<0.001), febrile neutropenia (24.7% vs. 2.5%; p<0.001) and infections (3.9% vs. 2.2%; p=0.05). This randomized study enrolled 1491 women with node- positive breast cancer, who received either Taxotere or 5-fluorouracil, in addition to doxorubicin and cyclophosphamide, following surgical tumor resection.
March 7, 2005
American Pharmaceutical Partners presented positive data from a phase III study of their recently approved drug Abraxane (albumin-bound paclitaxel particles), for the treatment of metastatic breast cancer at the 22nd Annual Miami Breast Cancer Conference. Study results yielded significant evidence of efficacy, with second-line patients receiving Abraxane experiencing significantly improved median survival times, vs. those receiving unmodified paclitaxel (56.4 weeks vs. 46.7 weeks; p=0.016); this response corresponded to a 29% reduction in risk of death. A non-significant improvement vs. paclitaxel was observed in the overall patient population, including both second-line-or-later subjects (65.0 weeks vs. 55.7 weeks). The drug maintained its advantageous tolerability profile, with no unexpected serious adverse events and no hypersensitivity reactions. This approved-therapy controlled study enrolled a total of 460 patients, who received either 260 mg/m2 Abraxane via 30 minute infusion with no premedication or 175 mg/m2 paclitaxel via 3 hour infusion with hypersensitivity-suppressing premedication including steroids and antihistamines.
June 14, 2004
Aesgen reported positive results of their phase III study of Saforis (L-glutamine) for the treatment of oral mucositis in cancer patients receiving chemotherapy. Results showed that Saforis significantly reduced the severity and duration of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy regimens versus placebo. Utilizing two sequential treatment cycles, subjects received either Saforis-then-placebo or placebo-then-Saforis. In the first cycle, Saforis subjects showed a 22% reduced incidence of moderate-to-severe oral mucositis, and when this group was switched to placebo during the second treatment cycle, incidence of oral mucositis was 36% below baseline. The multi-center study enrolled 326 evaluable subjects. Based on these results, Aesgen announced plans to file a NDA under their Fast Track designation in the near future.
GlaxoSmithKline reported positive interim results of their phase II study investigating lapatinib, an inhibitor of two receptor tyrosine kinases (ErbB1/EGFR and ErbB2), for the treatment of refractory metastatic breast cancer. Preliminary results from the first 41 subjects indicated that a once daily oral dose of lapatinib might effect an improved or stable disease state in women with breast cancer refractory to standard treatment regimens including Herceptin (trastuzumab). The study found that 46% (n=19) of the evaluated patients had stable or improved disease state at 8 weeks, and 24% (n=10) at 16 weeks. The ongoing multi-center, open label study plans to enroll a total of 80 women with breast cancer over-expressing ErbB2, all of whose disease had been refractory to treatment regimens including Herceptin, an FDA approved monoclonal ErbB2 antibody. If final results confirm the interim analysis, GlaxoSmithKline plans to use this trial to support ongoing trials of lapatinib in multiple ErbB2-expressing solid tumors.
ImClone Systems and Merck KGaA reported negative results from a phase III trial investigating IMC-BEC2, an anti-idiotypic monoclonal antibody cancer vaccine for the treatment of small cell lung cancer (SCLC). Results showed the vaccine trial did not meet its primary endpoint of survival. The international, randomized study was designed to assess the survival benefit of vaccination with IMC-BEC2 and the immune stimulant BCG over a two-year period. Subjects received IMC-BEC2/BCG vaccination or were only monitored in the observation arm. The study was conducted in collaboration with the European Organization for Research and Treatment of Cancer. Both companies intend to meet to discuss the future of the IMC-BEC2 development program.
OncoGenex and Isis announced positive results of a phase I study of OGX-011, an antisense clusterin inhibitor, for the treatment of prostate cancer. Results indicated that the drug achieved high concentration in target tissues and successfully dose-dependently down-regulated the expression of clusterin, a cell survival mediator. The study was designed to assess the bioavailability, tissue specificity and optimum dosing regimen of weekly IV infusions of OGX-011 in subjects with localized prostate cancer over 4 weeks. Immunostaining revealed availability of OGX-011 in the target tissue, and a 91% reduction in clusterin at the highest dose level (640 mg); this dose was determined to be optimum for future studies. The study enrolled a total of 25 subjects eligible for prostatectomy, all of whom underwent the surgery following the trial. OncoGenex and Isis planned to use the dosing information obtained in this trial to support the initiation of a phase II study later this year.
Therion Biologics reported results from two phase I trials investigating PANVAC-VF, a therapeutic cancer vaccine for the treatment of pancreatic cancer. The subcutaneously administered vaccine is designed to stimulate the immune system to target and destroy cancer cells expressing the carcinoembryonic antigen (CEA) and mucin -1 (MUC-1). Results showed a median overall survival of 7.9 months and at least 5.3 months, respectively, compared to an historical median overall survival of approximately 3.0 months. In addition, 33% of subjects in the study remain alive at 13 months. No serious adverse events related to the vaccines were reported. Common side effects included fever, chills and fatigue. The open label studies enrolled a total of 22 subjects with advanced (Stage III or IV) pancreatic cancer who had received prior chemotherapy. Due to these positive results, Therion will conduct a pivotal phase III trial with PANVAC-VF in the summer of 2004.
March 22, 2004
Pharmexa reported positive results from a phase I trial investigating HER-2 Protein AutoVac, a vaccine for the treatment of breast cancer. Data showed that the vaccine was well tolerated and that induced significant HER-2 specific antibodies in breast cancer patients. Results showed that six subjects demonstrated HER-2 specific antibody responses. Subjects received four injections of the vaccine formulated in a standard aluminium adjuvant. The study enrolled ten subjects and was conducted at the Ireland Cancer Center in Cleveland, Ohio and the Magee Women's Hospital in Pittsburgh, Pennsylvania. Full results will be reported at the 4th European Breast Cancer Conference (EBCC) in Hamburg, Germany. Pharmexa expects to commence phase II trials in the second half of 2004.
March 15, 2004
Pfizer reported positive results from a large phase IV trial investigating Aromasin (exemestane) for the treatment of breast cancer. Data showed subjects who switched to Aromasin after two or three years of taking tamoxifen were more likely to remain free of cancer. Results showed that subjects on Aromasin demonstrated a 32% reduction in the risk of recurrence of disease at three years, as compared to those continuing on tamoxifen. The double-blind, randomized study, called the Intergroup Exemestane Study (IES) enrolled over 4,700 post-menopausal women in 37 countries with breast cancer. Subjects received either Aromasin (25 mg) or continued on tamoxifen (20 mg) daily. Results were reported in March 2004 in the New England Journal of Medicine.
Schering-Plough reported results of a phase III trial investigating Caelyx, a pegylated liposomal doxorubicin hydrochloride for the treatment of breast cancer. Results demonstrated that Caelyx provided comparable efficacy in the first-line treatment of metastatic breast cancer with significantly reduced cardiac toxicity compared to doxorubicin. Primary efficacy endpoints were progression-free survival (PFS) and cardiac toxicity. Cardiac toxicity was defined by reductions in resting left ventricular ejection fraction assessed by serial MUGA (multigated radionuclide angiography) scans. In addition, the overall risk for developing a cardiac event was significantly reduced in subjects treated with Caelyx. The randomized study enrolled 509 subjects with metastatic breast cancer. Subjects received Caelyx (50 mg/m2) or doxorubicin (60 mg/m2). Results were reported in the March 2004 edition of Annals of Oncology.
December 8, 2003
Allos Therapeutics reported positive results from a phase III trial investigating RSR13 (efaproxiral), a radiation sensitizer for the treatment of cancer. The results demonstrate a significant survival benefit for women with breast cancer and brain metastases who received RSR13 plus whole brain radiation therapy (WBRT) versus WBRT alone. Data showed that subjects treated with RSR13 plus WBRT achieved a higher response rate in the brain than the control group (71.7% vs. 49.1). Subjects reported minimal serious adverse events with the most common being hypoxemia. The open-label, comparative, randomized study enrolled 538 subjects. Results were reported at the 26th Annual San Antonio Breast Cancer Symposium.
Genentech and Roche reported positive results from a phase II trial investigating Herceptin (Trastuzumab) in combination with Taxotere (docetaxel) as a first-line treatment for breast cancer. Results showed that the overall response rate for subjects with Herceptin plus docetaxel was significantly increased. Data showed that 61% of subjects who received Herceptin and docetaxel (100 mg/m2 every 3 weeks for at least 6 cycles) responded compared to 36% with docetaxel alone. The multi-center, randomized study enrolled 188 patients who had evidence of HER2-positive disease. Subjects received Herceptin (2mg/kg weekly) plus docetaxel or docetaxel alone. Results were reported at the 26th Annual San Antonio Breast Cancer Symposium.
October 13, 2003
American Pharmaceutical Partners and American BioScience reported positive results from a phase III trial investigating Abraxane (ABI-007), a nanoparticle albumin-bound paclitaxel for the treatment of metastatic breast cancer. Results demonstrated that Abraxane achieved higher anti-tumor activity and less toxicity than Taxol. Data showed a higher tumor response rate and a longer time to tumor progression in subjects receiving Abraxane. In addition, a secondary analysis showed the target lesion response rate was found to be significantly higher with Abraxane compared to Taxol. Both treatment regimens were well tolerated. The pivotal, randomized, controlled trial study enrolled 460 subjects and was designed to compare the safety and efficacy of Abraxane to Taxol, administered every three weeks. The dose of paclitaxel (260 mg/m2) was approximately 50% higher than that in the Taxol arm (175 mg/m2).
Hybridon reported positive results from a phase I trial investigating GEM 231, an antisense oligonucleotide for the treatment of solid tumors. Results showed low-grade fatigue in 57% of subjects that was cumulative over 4-6 weeks of repeated 5-day infusions and that rapidly reversed at the end of treatment. In addition, dose-related, reversible increases in serum transaminases and activated partial thromboplastin times were observed. The study enrolled 14 subjects who received escalating doses of GEM 231 in continuous intravenous infusion at 80 to 180 mg/m2/day. Results were reported in the September 15th issue of Clinical Cancer Research.
Procyon Biopharma reported positive interim results from a phase IIa trial investigating PCK3145, a natural prostate secretory derived protein for the treatment of prostate cancer. Results showed that two out of the four subjects in the first cohort showed a decline in PSA levels following treatment with PCK3145. Two subjects in the second cohort also showed an initial response in PSA reduction. Data also showed that four subjects who had plasma Matrix Metalloproteinase-9 (MMP-9) levels over 100 ug/L before treatment had reductions ranging from 34% to 90% after two cycles of treatment. The study showed no drug-related adverse effects. Results were reported at BioContact, Quebec City, Canada.
June 23, 2003
Biomira and Merck KGaA reported negative results from a phase III trial investigating Theratope, a vaccine for women with metastatic breast cancer. Results demonstrated that treatment did not meet statistical significance in the primary endpoints of time to disease progession and overall survival. One subset of women, placed on hormonal treatment following chemotherapy, showed a favourable trend in survival improvement. The randomized, double blind trial enrolled 1,030 subjects and was designed as a survival study. Theratope was well tolerated with the most common side effects being flu-like symptoms and local injection site reactions. Theratope is also being studied in a phase II study of women with metastatic breast cancer being treated with hormone therapy and a Phase II study in men and women for the treatment of colorectal cancer.
April 28, 2003
Allos Therapeutics reported mixed preliminary results from a phase III investigating RSR13 (efaproxiral), a radiation sensitizer agent for the treatment of brain metastases. Results showed that the difference in overall survival between subjects who received RSR13 plus whole brain radiation therapy (WBRT) and subjects who received only WBRT was not statistically significant. However, the trial did show a positive survival benefit among subjects with metastatic breast cancer. In addition, subjects receiving RSR13 plus WBRT experienced a 17.6% improvement in median survival length compared to subjects receiving WBRT alone (5.26 vs. 4.47 months). The randomized, open-label, pivotal study enrolled 538 subjects at more than 83 cancer sites worldwide.
January 13, 2003
BioVex reported positive preliminay results from a phase I trial investigating OncoVex (GM-Csf), an oncoloytic virus for the treatment of breast cancer and melanoma. Data showed that OncoVex caused tumor cells to secrete GM-CSF, which induced tumor necrosis and inflammation. Study results also showed the drug was well tolerated and presented anti-tumor activity at low doses. The primary goal of the study was to determine overall safety and to reveal indications of biological activity. The trial design included a single dose escalation phase to be given to groups of four subjects with metastatic cancer at each dose.
Genzyme Molecular Oncology reported positive results from a phase I/II trial investigating their melanoma cancer vaccine carried in an adenovirus vector. Data showed the vaccine produced clinical or immunologic responses in 71% (15/21) of the subjects treated. The study also showed that 38% of subjects (8/21) showed an immunological response at the sites of vaccination, 23.8% (5/21) experienced skin depigmentation and 14.2% exhibited asymptomatic changes in their retinas. Three subjects exhibited a clinical response, with one of them exhibiting an ongoing pathologic complete response after 18 months. The second subject demonstrated a partial response and the third showed stable disease after a ten-month duration. Treatment related adverse events were mild or moderate most of which were flu-like and flu-related symptoms. The study enrolled 27 subjects with locally advanced or metastatic melanoma, the majority of whom had received prior treatments.
November 11, 2002
GlaxoSmithKline reported positive results from a phase II trial of Navelbine (vinorelbine tartrate), a previously approved chemotherapy treatment, with the monoclonal antibody therapy Heceptin (trastuzumab) for the treatment of metastatic breast cancer. An overall response rate of 78% was observed with 4 complete and 25 partial responses reported. The study, designed to determine if the addition of Navelbine would increase the expected response rate to Herceptin, showed an improvement of 4-fold compared to historical data. Additionally, this combination extended the time to disease progression beyond the time shown in Herceptin alone. The multi-center, open-label trial enrolled 40 women with metastatic disease whose tumors over-expressed the HER2Neu oncogene, a growth-promoting protein linked to a poor prognosis in breast cancer.
September 16, 2002
Genentech reported that its phase III trials of Avastin in relapsed metastatic breast cancer subjects did not meet its primary efficacy endpoint. In this randomized study, 462 subjects with metastatic breast cancer, previously treated with both anthracycline and taxane-based chemotherapy received Avastin with Xeloda (capecitabine) or Xeloda alone. The results, in the secondary treatment, did achieve statistical significance. However, it did not translate into benefit in progression-free survival or 12-month survival. Based on the positive results of Avastin's overall phase II trials, Genetech will continue to test Avastin for other indications.
February 4, 2002
Study results indicate that Novartis' Femara (letrozole) is more effective than AstraZeneca's Arimidex (anastrozole) in inhibiting total body aromatization and suppressing plasma estrogen levels. The randomized trial included 12 postmenopausal women with metastatic breast cancer whose disease was suitable for treatment with an aromatase inhibitor. Results showed that on-treatment levels of aromatization were detectable in 11 of 12 subjects during treatment with Arimidex; in comparison, they were undetectable in all 12 subjects during treatment with Femara. Femara versus Arimidex treatment also suppressed mean plasma estrogen levels as follows: estrone (84.3% vs. 81.0%), estrone sulfate (98.0% vs. 93.5%) and estradiol (87.8% vs. 84.9%).
December 17, 2001
Phase III trial results indicate that first-line therapy with Novartis' Femara (letrozole) improves survival of postmenopausal women with locally advanced or metastatic breast cancer compared to tamoxifen. The randomized, double-blind trial consisted of 907 postmenopausal women, with 453 receiving Femara and 454 receiving tamoxifen. At one and two years, data demonstrated that Femara produced a statistically significant survival advantage compared to tamoxifen. Additionally, in comparison to subjects receiving tamoxifen, those on Femara had a 78% greater chance of responding to treatment. In terms of disease progression, Femara was shown to delay progression for a median of 9.4 months compared to 6.0 months for tamoxifen.